Global Blood Therapeutics (GBT) Presents GBT440 Data in Sickle Cell Disease at ASCAT

October 7, 2016 9:08 AM EDT

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Global Blood Therapeutics, Inc. (GBT) (NASDAQ: GBT), a biopharmaceutical company developing novel therapeutics for the treatment of grievous blood-based disorders with significant unmet needs, today announced that an encore presentation of the GBT440-001 study data supporting the durability, safety and mechanism of action of GBT440 in sickle cell disease were presented today in an oral session at the Academy for Sickle Cell and Thalassemia (ASCAT) 10th Anniversary Conference in London.

“Hemoglobin oxygen affinity modulation is a very promising approach for modifying disease in SCD because it intervenes on the fundamental pathologic process- HbS polymerization. GBT440 is an exciting hemoglobin modifier in development because of excellent specificity and pharmaceutical properties resulting in both increased potency and an improved safety profile. Over three months of dosing, GBT440 has shown profound and durable reductions in hemolysis and sickling, which provides further support that this novel hemoglobin modifier has the potential to be a once-daily treatment for patients with sickle cell disease,” said Dr. Jo Howard, consultant hematologist and head of the red cell/sickle cell service at Guy's and St Thomas' NHS Foundation Trust in London. “Further, given that all 34 SCD patients dosed with GBT440 for 28 to 90 days have shown a positive hematologic response, I believe that GBT440 could potentially transform the treatment of this devastating disease.”

“The data showing a rapid and durable reduction in hemolytic anemia and sickling over 90 days support both the mechanism of action and the efficacy profile of GBT440 as a potentially disease-modifying therapy for SCD,” said Ted W. Love, M.D., president and chief executive officer of GBT. “We are currently in discussions with the FDA regarding details of our regulatory path forward for GBT440 in SCD. Based on these promising results, we believe that GBT440 has the potential to improve the clinical course of sickle cell disease and look forward to exploring this further in a pivotal trial that remains on track to initiate by year-end. In addition, we look forward to presenting our full 90 day data for our 900 mg per day cohort at the upcoming American Society of Hematology meeting.”

Design of Ongoing Phase 1/2 GBT440-001 TrialGBT440-001 is a randomized, placebo-controlled, double-blind, single and multiple ascending dose study evaluating the safety, tolerability, PK and PD of GBT440 in both healthy subjects and patients with SCD. The study is being conducted in three parts: Part A (single dose administration), Part B (multiple dose administration, daily for 15 days in healthy subjects and 28 days in SCD patients) and Part C (multiple dose administration, daily for 90 days in SCD patients).

Data Presentation HighlightsThe data presented at ASCAT were previously presented at the European Hematology Association's 21st Congress in June.

In the six patients treated with GBT440 700 mg/day for 90 days, results showed:

  • A durable reduction in hemolysis (red blood cell destruction) from baseline to day 90, as evidenced by a rapid and sustained reduction in bilirubin starting as early as day 4 and continuing through day 90 (median decrease of greater than 35% compared with an increase of approximately 20% with placebo).
  • A median 1.1 g/dL increase in hemoglobin concentration with GBT440 treatment compared with a 0.2 g/dL decrease with placebo.
  • A median decrease of approximately 20% in reticulocyte count compared with an approximately 20% increase with placebo, suggesting that the observed increase in hemoglobin is due to a decrease in hemolysis.
  • Steady improvement in hemoglobin and reticulocyte counts through day 60 to 90 after initial variability of hemoglobin and reticulocytes during the first 3-6 weeks (likely due to bone marrow adjusting to dramatic reduction in hemolysis).
  • A sustained reduction in irreversibly sickled cells, with a median decrease of approximately 70% within 90 days compared to an increase of approximately 15% with placebo.
  • GBT440 was well tolerated over 90 days of dosing. The most common adverse event was headache, seen in both the placebo and GBT440 arms. There have been no drug-related serious adverse events.

Complete 28-day results from three dosing cohorts of GBT440 (500 mg [n=10]), 700 mg [n=12] and 1,000 mg administered as 500 mg BID [n=5]) showed:

  • A consistent beneficial effect was seen in at least one key parameter: hemolysis, reticulocytosis or sickle cell counts.
  • The therapeutic target between 10-30% Hb modification was achieved at GBT440 doses ≥500 mg.

GBT440-001 Overall Safety SummaryAcross the GBT440 clinical development program, GBT440 has now been dosed in 252 adults, including 128 subjects in multiple dosing cohorts up to 90 days. It has been shown to be well tolerated with no drug-related serious adverse events. There has been no evidence of tissue hypoxia in healthy subjects up to approximately 40% Hb modification or in SCD subjects up to approximately 30% Hb modification.

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